cDNAs representing Poly A+RNAs whose expression is specifically induced in SV40 transformed human epidermal keratinocytes have been isolated from cDNA libraries by subtraction hybridization to remove sequences expressed in the normal keratinocytes as reported previously. Two such DNAs, designated E12 and E13, have been examined with particular interest because: 1) unlike other candidate cDNAs these sequences were completely undetectable in normal epithelial cells or in normal human fibroblasts, and, 2) northern blot analysis showed that the corresponding mRNAs were found to be induced to high levels of expression not only in the viral transformants also in several cell lines derived from squamous cell carcinomas and malignant tumors of the breast and cervix. Sequence analysis of E12 and E13 revealed no sequence homology between these sequences and any other sequence recently catalogued in either the Genbank (release 81) or EMBL sequence databanks. These results suggests that induction of expression of the genes corresponding to H2 and E13 is a common, and possibly an essential step in the transformation process in both viral and spontaneously transformed epithelial cells.